PGE.sub.2 has been known as metabolite in the arachidonate cascade. In addition, the recent progress in the molecule biological technology makes the existence of three PGE.sub.2 receptors clear as shown in the following and have been making the relationship between each receptor and appearance of biological activity clear. For example, EP.sub.1 receptor may cause contraction of the smooth muscle of digestive canal or bronchus etc. and promote the release of neurotransmitter. The representative activity of EP.sub.2 receptor is relaxation of smooth muscle of bronchus or ileum etc. or vasodilatation and reduce of the blood pressure due to relaxation of vascular smooth muscle.
As the activity of EP.sub.3 receptor, uterine muscle contraction, suppression of gastric acid secretion, inhibition of reabsorption of water and ion by vasopressin in renes, inhibition of fat decomposition in fat tissue, inhibition of release of neurotransmitter and glucose-decomposition by gulcagon in liver cell etc. have been known. In addition, recently, the existence of fourth receptor is suggested. (Biochemistry Vol. 66, No. 3, pp. 218-231 (1994))
Therefor, to antagonize PGE.sub.2 receptor means to suppress the effects above mentioned, so such an activity is linked to inhibit diuretic, to inhibit hyperlipemia, to inhibit reduce of blood sugar, to inhibit uterine contraction, to have analgesic action, to inhibit digestive peristalsis, to induce sleep. Therefor, PGE.sub.2 receptor antagonists are considered to be useful as anti-hyperlipemia, for the prevention of abortion, for analgesics, or as antidiarrheals or sleep inducer.
To agonize for PGE.sub.2 receptor means to promote the effects above mentioned, so such an activity is linked to have diuretic, to promote hyperlipemia, to promote reduce of blood sugar, to contractile uterine, to promote digestive peristalsis, to suppress gastric acid secretion or to reduce blood pressure. Therefor, PGE.sub.2 receptor agonists are considered to be useful for diuretic, anti-diabetes, abortient, cathartics, antiulcer, anti-gastritis or antihypertensive.
In such a background, a lot of compounds which agonize or antagonize for PGE.sub.2 receptors have been proposed.
For example, in the specification of EP-0657422, it is disclosed that the compounds of the formula (A) ##STR3##
In the specification of EP-0578847 (corresponding to JP Patent Application Kokai Hei 6-25074), it is disclosed that the compounds of the formula (B) ##STR8##
(ii) C1-8 alkyl substituted by 1 or 2 of benzene ring, C4-7 cycloalkyl or 4-7 membered monocyclic ring containing one nitrogen, PA2 (i) hydrogen, PA2 (ii) -(C1-4 alkylene)-COOR.sup.1 in which R.sup.1 is hydrogen or C1-4 alkyl, PA2 (iii) -(C1-4 alkylene)-CONR.sup.2 R.sup.3 in which R.sup.1 and R.sup.3 each, independently, is hydrogen or C1-4 alkyl, PA2 (iv) -(C1-4 alkylene)-OH, PA2 (v) -(C1-4 alkylene)-tetrazolyl or PA2 (vi) -(C1-4 alkylene)-CN; PA2 (ii) C1-6 alkylene; PA2 (ii) -(CH.sub.2).sub.m --CH.dbd.CH--(CH.sub.2).sub.n -- in which m is 0 or an integer of 1-3, n is 0 or an integer of 1-3 or PA2 (iii) -(CH.sub.2).sub.x --CH(OH)--(CH.sub.2).sub.y -- in which x is an integer of 1-3, y is 0 or an integer of 1-3; ##STR11## PA2 (1) when G is --SO-- or --SO.sub.2 --, M is neither ##STR13## PA2 (2) when m in L is 0, G is --SO-- or --SO.sub.2 --, PA2 (3) when n in L is 0, M is ##STR14## PA2 (4) when y in L is 0, M is ##STR15## PA2 (5) when A is hydrogen, L is --(CH.sub.2).sub.m --CH.dbd.CH--(CH.sub.2).sub.n -- in which m and n are the same meaning as hereinbefore defined, or --(CH.sub.2).sub.x --CH(OH)--(CH.sub.2).sub.y in which x and y are the same meaning as hereinbefore defined, and PA2 (6) tetrazolyl in A is ##STR16## PA2 (1) 1-[2-(5-hydroxy-1-naphthyl)ethylthio]-3-phenoxy-2RS-propanol, PA2 (2) 1-[2-(5-hydroxy-1-naphthyl)ethylsulfinyl]-3-phenoxy-2RS-propanol, PA2 (3) 1-[2-(5-hydroxy-1-naphthyl)ethylsulfonyl]-3-phenoxy-2RS-propanol, PA2 (4) 1-[2-(5-hydroxy-1-naphthyl)ethylthio]-3-phenoxy-2R-propanol, PA2 (5) 1-[2-(5-hydroxy-1-naphthyl)ethylthio]-3-phenoxy-2S-propanol, PA2 (6) 1-(5-hydroxy-1-naphthyl)methylthio-3-phenoxy-2RS-propanol, PA2 (7) 1-(5-hydroxy-1-naphthyl)methylsulfinyl-3-phenoxy-2RS-propanol, PA2 (8) 1-(5-hydroxy-1-naphthyl)methylsulfonyl-3-phenoxy-2RS-propanol, PA2 (9) 2-[3-(5-hydroxy-1-naphthyl)propyithio]-1-phenyl-1RS-ethanol, PA2 (10) 2-[3-(5-hydroxy-1-naphthy)propylsulfinyl]-1-phenyl-1RS-ethanol, PA2 (11) 2-[3-(5-hydroxy-1-naphthyl)propylsulfonyl]-1-phenyl-1RS-ethanol, PA2 (12) 1-(5-hydroxy-1-naphthyl)thio-3-phenoxy-2RS-propanol, PA2 (13) 1-(5-hydroxy-1-naphthyl)sulfinyl-3-phenoxy-2RS-propanol, PA2 (14) 1-(5-hydroxy-1-naphthyl)sulfonyl-3-phenoxy-2RS-propanol, PA2 (15) 1-[2-(5-hydroxy-1-naphthyl)ethylthio]-3-(4-chlorophenoxy)-2RS-propanol, PA2 (16) 1-[2-(5-hydroxy-1-naphthyl)ethylthio]-3-(4-methylphenoxy)-2RS-propanol, PA2 (17) 1-[2-(5-hydroxy-1-naphthyl)ethylthio]-3-(4-methoxyphenoxy)-2RS-propanol, PA2 (18) 1-[2-(5-hydroxy-1-naphthyl)ethylthio]-3-diphenylmethoxy-2RS-propanol, PA2 (19) 1-[2-(5-hydroxy-1-naphthyl)ethylthio]-3-[1-phenyl-1-(4-chlorophenyl)-metho xy]-2RS-propanol, PA2 (20) 1-[2-(5-hydroxy-1-naphthyl)ethylthio]-3-phenylthio-2RS-propanol, PA2 (21) 1-(5-hydroxy-1-naphthyl)methylthio-3-diphenylmethoxy-2RS-propanol, PA2 (22) 1-(5-hydroxy-1-naphthyl)methylthio-3-[1-phenyl-1-(4-chlorophenyl)-methoxy] -2RS-propanol, PA2 (23) 2-{5-[2-(2RS-hydroxy-3-phenoxypropylthio)ethyl]-1-naphthyloxy}-acetic acid methyl ester, PA2 (24) 2-{5-[2-(2RS-hydroxy-3-phenoxypropylsulfinyl)ethyl]-1-naphthyloxy}acetic acid methyl ester, PA2 (25) 2-{5-[2-(2RS-hydroxy-3-phenoxypropylsulfonyl)ethyl]-1-naphthyloxy}-acetic acid methyl ester, PA2 (26) 2-{5-[2-(2R-hydroxy-3-phenoxypropylthio)ethyl]-1-naphthyloxy}acetic acid methyl ester, PA2 (27) 2-{5-[2-(2S-hydroxy-3-phenoxypropylthio)ethyl]-1-naphthyloxy}acetic acid methyl ester, PA2 (28) 2-[5-(2RS-hydroxy-3-phenoxypropylthio)methyl-1-naphthyloxy]acetic acid methyl ester, PA2 (29) 2-[5-(2RS-hydroxy-3-phenoxypropylsulfinyl)methyl-1-naphthyloxy]acetic acid methyl ester, PA2 (30) 2-[5-(2RS-hydroxy-3-phenoxypropylsulfonyl)methyl-1-naphthyloxy]acetic acid methyl ester, PA2 (31) 2-{5-[3-(2RS-hydroxy-2-phenylethylthio)propyl]-1-naphthyloxy}acetic acid methyl ester, PA2 (32) 2-{5-[3-(2RS-hydroxy-2-phenylethylsulfinyl)propyl]-1-naphthyloxy}acetic acid methyl ester, PA2 (33) 2-{5-[3-(2RS-hydroxy-2-phenylethylsulfonyl)propyl]-1 -naphthyloxy}acetic acid methyl ester, PA2 (34) 2-[5-(2RS-hydroxy-3-phenoxypropylthio)-1-naphthyloxy]acetic acid methyl ester, PA2 (35) 2-[5-(2RS-hydroxy-3-phenoxypropylsulfinyl)-1-naphthyloxy]acetic acid methyl ester, PA2 (36) 2-[5-(2RS-hydroxy-3-phenoxypropylsulfonyl)-1-naphthyloxy]acetic acid methyl ester, PA2 (37) 2-[5-(3-styrylsulfonylpropyl)-1-naphthyloxy]acetic acid methyl ester, PA2 (38) 2-[5-(3-styrylsulfinylpropyl)-1-naphthyloxy]acetic acid methyl ester, PA2 (39) 2-{5-[2-(2RS-hydroxy-3-(4-chlorophenoxy)propylthio)ethyl]-1-naphthyloxy}ac etic acid methyl ester, PA2 (40) 2-{5-[2-(2RS-hydroxy-3-(4-methylphenoxy)propylthio)ethyl]-1-naphthyloxy}ac etic acid methyl ester, PA2 (41) 2-{5-[2-(2RS-hydroxy-3-(4-methoxyphenoxy)propylthio)ethyl]-1-naphthyloxy}a cetic acid methyl ester, PA2 (42) 2-{5-[2-(2RS-hydroxy-3-diphenylmethoxypropylthio)ethyl]-1-naphthyloxy}-ace tic acid methyl ester, PA2 (43) 2-{5-[2-(2RS -hydroxy-3-(1-phenyl-1-(4-chlorophenyl)methoxy)propylthio)-ethyl]-1-naphth yloxy}acetic acid methyl ester, PA2 (44) 2-{5-[2-(2RS-hydroxy-3-phenylthiopropylthio)ethyl]-1-naphthyloxy}acetic acid methyl ester, PA2 (45) 2-[5-(2RS -hydroxy-3-diphenylmethoxypropylthio)methyl-1-naphthyloxy]-acetic acid methyl ester, PA2 (46) 2-{5-[2RS-hydroxy-3-(1-phenyl-1-(4-chlorophenyl)methoxy)propylthio]-methyl -1-naphthyloxy}acetic acid methyl ester, PA2 (47) 2-{5-[2-(2RS-hydroxy-3-phenoxypropylthio)ethyl]-1-naphthyloxy}-acetic acid, PA2 (48) 2-{5-[2-(2RS -hydroxy-3-phenoxypropylsulfinyl)ethyl]-1-naphthyloxy}acetc acid, PA2 (49) 2-{5-[2-(2RS-hydroxy-3-phenoxypropylsulfonyl)ethyl]-1-naphthyloxy}-acetic acid, PA2 (50) 2-{5-[2-(2R-hydroxy-3-phenoxypropylthio)ethyl]-1-naphthyloxy}-acetic acid, PA2 (51) 2-{5-[2-(2S-hydroxy-3-phenoxypropylthio)ethyl]-1-naphthyloxy}-acetic acid, PA2 (52) 2-[5-(2RS-hydroxy-3-phenoxypropylthio)methyl-1-naphthyloxy]-acetic acid, PA2 (53) 2-[5-(2RS-hydroxy-3-phenoxypropylsulfinyl)methyl-1-naphthyloxy]acetic acid, PA2 (54) 2-[5-(2RS-hydroxy-3-phenoxypropylsulfonyl)methyl-1-naphthyloxy]acetic acid, PA2 (55) 2-{5-[3-(2RS-hydroxy-2-phenylethylthio)propyl]-1-naphthyloxy}acetic acid, PA2 (56) 2-[5-(2RS-hydroxy-3-phenoxypropylthio)-1-naphthyloxy]acetic acid, PA2 (57) 2-[5-(2RS-hydroxy-3-phenoxypropylsulfinyl)-1-naphthyloxy]acetic acid, PA2 (58) 2-[5-(2RS-hydroxy-3-phenoxypropylsulfonyl)-1-naphthyloxy]acetic acid, PA2 (59) 2-[5-(3-styrylsulfinylpropyl)-1-naphthyloxy]acetic acid, PA2 (60) 2-[5-(3-styrylsulfonylpropyl)-1-naphthyloxy]acetic acid, PA2 (61) 2-{5-[2-(2RS-hydroxy-3-(4-chlorophenoxy)propylthio)ethyl]-1-naphthyloxy}ac etic acid, PA2 (62) 2-{5-[2-(2RS-hydroxy-3-(4-methylphenoxy)propylthio)ethyl]-1-naphthyloxy}ac etic acid, PA2 (63) 2-{5-[2-(2RS-hydroxy-3-(4-methyoxyphenoxy)propylthio)ethyl]-1-naphthyloxy} acetic acid, PA2 (64) 2-{5-[2-(2RS-hydroxy-3-diphenylmethoxypropylthio)ethyl]-1-naphthyloxy}-ace tic acid, PA2 (65) 2-{5-[2-(2RS-hydroxy-3-phenylthiopropylthio)ethyl]-1-naphthyloxy}acetic acid, PA2 (66) 2-[5-(2RS-hydroxy-3-diphenylmethoxypropylthio)methyl-1-naphthyloxy]acetic acid, PA2 (67)1-cyanlomethoxy-5-[2-(2RS-hydroxy-3-phenoxypropylthio)-ethyl]naphthalen e, PA2 (68)1-cyanomethoxy-5-{2-[2RS-hydroxy-3-(4-chlorophenoxy)propylthio]ethyl}-n aphthalene, PA2 (69)1-cyanomethoxy-5-{2-[2RS-hydroxy-3-(4-methylphenoxy)propylthio]ethyl}na phthalene, PA2 (70)1-cyanomethoxy-5-{2-[2RS-hydroxy-3-(4-methoxyphenoxy)-propylthio]ethyl} naphthalene, PA2 (71)1-cyanomethoxy-5-[2-(2RS-hydroxy-3-diphenylmethoxypropylthio)-ethyl]nap hthalene, PA2 (72)1-cyanomethoxy-5-[2-(2RS-hydroxy-3-phenylthiopropylthio)-ethyl]naphthal ene, PA2 (73)1-cyanomethoxy-5-(2RS-hydroxy-3-diphenylmethoxypropylthiomethyl)-naphth alene, PA2 (74)2-{5-[2-(2RS-hydroxy-3-(1-phenyl-1-(4-chlorophenyl)methoxy)propylthio)- ethyl]-1-naphthyloxy}ethanol, PA2 (75)2-{5-[2-(2RS-hydroxy-3-phenylaminopropylthio)ethyl]-1-naphthyloxy}ethan ol, PA2 (76)1-(tetrazol-5-ylmethoxy)-5-{2-{2RS-hydroxy-3-(4-methyoxyphenoxy)-propyl thio]ethyl}naphthalene, PA2 (77) N-methyl-{5-[2RS-hydroxy-3-(1-phenyl-1-(4-chlorophenyl)methoxy)-propylthio ]methyl-1-naphthyloxy}acetic acid amide, PA2 (78) 1-{2-[5-hydroxy-1-(1,2,3,4-tetrahydronaphthyl)]ethylthio}-3-phenoxy-2RS-pr opanol, PA2 (79) 2-{5-[2-(2RS-hydroxy-3-phenoxypropylthio)ethyl]-1-(5,6,7,8-tetrahydro-naph thyloxy)}acetic acid methyl ester, PA2 (80) 2-{5-[2-(2RS-hydroxy-3-phenoxypropylthio)ethyl]-1-(5,6,7,8-tetrahydro-naph thyloxy)}acetic acid or PA2 (81) 1-cyanomethoxy-5-[2-(2RS-hydroxy-3-phenoxypropylthio)ethyl]-5,6,7,8-tetrah ydronaphthalene, PA2 (1) 1-[2-(5-hydroxy-1-naphthyl)ethoxy]-3-phenoxy-2RS-propanol, PA2 (2) 2-{5-[2-(2RS-hydroxy-3-phenoxypropoxy)ethyl]-1-naphthyloxy}acetic acid methyl ester or PA2 (3) 2-{5-[2-(2RS-hydroxy-3-phenoxypropoxy)ethyl]-1-naphthyloxy}acetic acid, PA2 (1)1-[2-(5-hydroxy-1-naphthyl)ethylamino]-3-phenoxy-2RS-propanol or PA2 (2) 2-{5-[2-(2RS-hydroxy-3-pheoxypropylamino)ethyl]-1-naphthyloxy}acetic acid, PA2 (i) -(C1-4 alkylene)-COOR.sup.1a in which R.sup.1a is C1-4 alkyl, PA2 (ii) -(C1-4 alkylene) --OR.sup.5, in which R.sup.5 is tetrahydropyranyl, PA2 (iii) -(C1-4 alkylene) --CONR.sup.2 R.sup.3, PA2 (iv) -(C1-4 alkylene)-tetrazolyl or PA2 (v) -(C1-4 alkylene)-CN, PA2 2) hydrogen when G.sup.3 is --O-- or --NR.sup.4a -- in which R.sup.4a is C1-4 alkyl, PA2 3) NH-protecting group as defined hereinbefore when G.sup.3 is --NH--
is (iii) or (iv), --(CH.sub.2)p.sup.B -- and .dbd.CH--(CH.sub.2)s.sup.B -- is bonded at the position a or b on the ring, and the ring in R.sup.3B may be substituted by one to three of C1-4 alkyl, C1-4 alkoxy, halogen, nitro or trihalomethyl, are useful as PGI.sub.2 agonist.
In the specification of JP Patent Application Kokai Sho 61-267532, it is disclosed that the compounds of the formula (D) EQU Ar.sup.1D -X.sup.D -Ar.sup.D -Z.sup.D -(R.sup.D)n.sup.D ' (D)
In addition, in the specification of (E) U.S. Pat. No. 4,327,022, (F) JP Patent Application Kokai Sho 50-89352 and (G) U.S. Pat. No. 3,930,672, it is disclosed that the naphthol derivatives are useful as (1) cardiotonic or anti-bacterial agents, (2) analgesic, anti-inflammatory and antipyretic agent and (3) starting material of the compound related to copy paper, respectively.